Genomic instability, a hallmark of cancer cells, cart be produced by cytotoxic drugs and ionizing radiation.and occurs for multiple reasons, including loss of cell cycle checkpoint control or defects in the DNA damage repair machinery. The lack of maintenance of genomic integrity provides a mechanism for both tumor progression and tumor heterogeneity. A major process involved in repairing DNA damage and preventing cancer formation due to chromosomal fragmentation, translocations or deletions is the double strand break (DSB) repair pathway. We believe that the alteration in expression of tumor suppressor genes involved in DSB and genes directly involved with DNA double strand break repair may provide information on how to treat a particular cancer. We hypothesize that the expression levels and/or cellular localization of proteins involved in double strand break repair are clinically important biological features that lead to improved treatment response to cytotoxic chemotherapy and better outcome in breast and other cancers. To test this, we will generate the biochemical reagents to enable us and other researchers to determine if the expression or production of specific proteins involved in DSB are altered by chemotherapeutic drugs in cancer cells. This information will facilitate the determination of unique prognostic and predictive indicators and help clinicians decide whether a given patient should receive a specific chemotherapy. PROPOSED COMMERCIAL APPLICATIONS: Antibodies against these proteins involved in DNA repair will be useful in dissecting and understanding the pathways involved in the cellular response to DNA damage. We can anticipate that one or more of these proteins may be important in specific cancers, including prostrate, colon and breast cancer and the resulting antibodies will be useful tools in the future diagnosis of these diseases.